We have shown that quiescent hamster sperm from the epididymis lack cAMP, and that their motility is activated by the initiation of cAMP synthesis. This event is triggered by mixing with calcium, and ion which although not present in epididymal fluid, is secreted in large amounts by the prostate. We have also observed that external cyclic nucleotides can by-pass this requirement for calcium ion to activate motility, but that, due to the presence of a previously undetected cAMP- phosphodiesterase in epididymal fluid, this does not happen in vivo. We propose to determine how general this control phenomenon is by determining whether calcium ion triggers the activation of sperm motility in other mammals and what the calcium ion distribution in male reproductive fluids is. We also will inquire whether calcium and cyclic nucleotides function as first messengers in the activation of cAMP synthesis by sperm adenyl cyclase; and what the origin, properties and contraceptive significance of epididymal fluid cAMP-phosphodiesterase is. We have found that motile hamster sperm can apparently be diluted infinitely in the presence of a small molecule from epididymal fluid. This factor completely abolishes the classical sperm dilution effect. We propose to isolate and identify this significant small molecule. We will evaluate its reproductive tract and species distribution. We will also inquire why it is essential for sperm survival, whether it can be used to make superior diluents for sperm preservation and whether it can be chemically inactivated to effect contraception.